Phase 1 clinical trial evaluating the safety and preliminary efficacy of autologous NK cells combined with T lymphocytes in patients with recurrent solid tumors

Abstract

Patients with advanced solid tumors who progress after standard therapies have limited treatment options. SDH-Combi is an autologous cellular immunotherapy integrating natural killer cells and tumor-primed T lymphocytes, designed to address tumor heterogeneity and immune escape through complementary immune mechanisms. This single-arm, phase 1 study evaluated SDH-Combi in patients with recurrent or progressive solid tumors. SDH-Combi was administered every 2 weeks for up to eight infusions. The primary endpoint was safety and tolerability in all treated patients ( N = 9): Safety was assessed as treatment-emergent adverse events graded by CTCAE v5.0 with investigator-assigned causality, and tolerability as the proportion of patients completing all eight planned infusions, the relative dose intensity, and discontinuation due to toxicity. Secondary endpoints were objective response rate, disease control rate, progression-free survival, and overall survival, with tumor response evaluated according to RECIST v1.1. Quality of life (QoL), assessed with the EORTC QLQ-C30, was an exploratory endpoint. Nine patients received at least one infusion. For the primary endpoint, no grade ≥ 3 treatment-related adverse event occurred (0 of 9; 95% CI, 0.0–33.6) and no patient discontinued because of toxicity; six of nine patients (66.7%) completed all eight planned infusions and 64 of 72 planned infusions (88.9%) were administered . No cytokine release syndrome, anaphylaxis, or treatment-related serious adverse events occurred. One patient (Patient 8) experienced a grade 4 anemia event (hemoglobin nadir 4.5 g/dL) judged unlikely related to study therapy; all other events were grades 1–2. In the full analysis set ( N = 9), the disease control rate was 66.7%, and the objective response rate was 11.1%. Mean changes in five of the six functional domains (global health status/QoL, physical, role, emotional, and social functioning) and in all nine symptom domains met the EORTC minimal clinically important difference threshold of ≥ 10 points. The change in constipation (− 11.1 points) was marginal, and cognitive functioning did not reach the threshold. While median overall survival had not been reached at the safety assessment time point and five of nine patients had died by the 14 January 2026 follow-up, formal statistical inference remains limited by the small, single-arm sample. SDH-Combi was feasible and well tolerated, with preliminary signals of disease stabilization and QoL improvement in previously treated patients (1–3 prior systemic lines). These findings support further clinical evaluation of this biologically rational combination cellular immunotherapy.